CAMPATH-1H IN RHEUMATOID-ARTHRITIS - AN INTRAVENOUS DOSE-RANGING STUDY

Forty-one patients with active and refractory rheumatoid arthritis (RA ) received a total of 100, 250 or 400 mg of CAMPATH-1H (CAMPATH is a t rademark of Glaxo-Wellcome group companies, registered in the US Paten t and Trademark Office) over 5 or 10 days in an open, uncontrolled stu dy. Following therapy, patients were monitored for adverse effects and disease activity for 6 months. Therapy was associated with prolonged peripheral blood lymphopenia in all dosing cohorts. During the month i mmediately following therapy, lymphopenia was most profound in the 400 mg cohorts. The first dose of monoclonal antibody (Mab) was associate d with a 'flu'-like syndrome, more pronounced at higher initial doses. One patient developed haemolytic-uraemic syndrome. There were a numbe r of dose-related infections during the early post-treatment period an d one fatal opportunistic infection which followed additional immunosu ppressive therapy. Antiglobulin responses developed in 9 of 31 patient s tested. The majority of patients showed symptomatic improvement foll owing therapy and 20% of patients maintained a 50% Paulus response at 6 months, all of whom were in the 250 or 400 mg cohorts. CAMPATH-1H ap pears to be an effective treatment for RA. Allowing for the small numb er of patients treated, infections were more common with higher doses, although this was not true for adverse events overall, and therapeuti c responses were more sustained at higher dosing levels. The broad spe cificity of CAMPATH-1H may be appropriate for the immunotherapy of RA and future studies should aim to define a dose with an optimal therape utic ratio.